We intend to continue our studies in the arthritis model, induced by immunization of rats with cartilage collagen, as well as our clinical investigations. By antigen-presentation techniques, we hope to gain additional insights into the role of T and B cells in the rat arthritis. Neuroendocrine studies may elucidate the mechanism(s) by which stress modalities can modulate the development and severity of arthritis in rats immunized with collagen. Pathology studies, using transmission and scanning electron microscopy, as well as immunofluorescence, should determine the sequence of intrasynovial evets following injection of type II collagen. As a further correlate to our human studies, the role of autoimmune responses to homologous type III collagen in the rat model will be explored. The suitability of the model to evaluate pharmacologic agents with potential anti-rheumatic effects in humans will be addressed. We will also continue to study the mechanism(s) by which collagen induces production of monocyte-derived collagenase stimulating factor and prostaglandin E2 production by blood mononuclear cells.